The goal of this program is to perform directed investigations into the evolution of lasting, protective Immune responses in humans in order to better understand the requirements of effective vaccines and adjuvants. This application is submitted to obtain funding for a Cooperative Center on Human Immunology at The Rockefeller University. Our program is highly integrated and is based on long-term, productive collaborations between the PIs on defining underlying principles of human immunology, utilizing the infrastructure of the Rockefeller University Hospital, the Zanvil Cohn Vaccine Center and the Rockefeller University Clinical and Translational Science Award (CTSA). The proposed research projects are designed as hypothesis-testing, mechanistic studies, examining novel aspects of the activation and regulation of human immune responses in the context of vaccination against infectious disease. The participating investigators are pioneers in identifying and characterizing basic mechanisms of the human immune response, having contributed to the initial characterizations of the dendritic cell, the diversity of IgG antibody effector functions ad description of Fc receptors as mediators of immunity, the development of the first models for study of the hepatitis C virus and the Identification of multiple HCV receptors. While significant progress in basic immunology research over the last three decades has resulted in numerous medical advances, a much more substantial understanding of coordinated molecular mechanisms involved in eliciting Immunity will be required to enable judicious vaccine design, particularly for diseases for which no vaccines currently exits. The objective of this proposal is o draw on the broad expertise in immunity and infectious diseases within the collaborating laboratories to define the contributions of critical components, such as dendritic cells, T follicuar helper cells, monocytes and immune complexes in the generation and maintenance of effective immune responses to infectious agents.